Over the past decade, much research has been devoted to developing new and useful devices for delivering beneficial agents to agent receptor environments of use. For example, Theeuwes U.S. Pat. No. 3,760,984 discloses an osmotic delivery device comprising an inner collapsible container carrying on its outer surface a layer of an osmotic solute and a surrounding layer of a polymer permeable to fluid and impermeable to solute. Wichterle U.S. Pat. No. 3,971,376 discloses a device comprising a capsule having a unitary wall formed of a substantially noncollapsible elastic material that maintains a constant volume and adapted to be implanted subcutaneously. A textile fabric may be imbedded in the capsule wall. The fabric strengthens the wall and acts as a reinforcement. Eckenhoff et al. U.S. Pat. No. 3,987,790 discloses another osmotic delivery device which contains an outer shape-retaining membrane which is sufficiently rigid to be substantially undeformed by the hydrostatic pressure exerted by water permeating through the membrane.
Higuchi et al. U.S. Pat. No. 3,995,631 discloses a device (FIG. 4) comprising an inner flexible bag containing a drug formulation. The bag separates the drug from an osmotically effective solute material. Both the drug and the solute are contained within a housing having an exterior wall that is, at least in part, semipermeable. Nakano et al. U.S. Pat. No. 3,995,632 discloses a similar device which incorporates a movable barrier within the housing. The barrier divides the housing into two compartments, one containing the solute and the other containing the drug. The solute-containing compartment has an exterior wall that is, at least in part, semipermeable. This compartment acts as an osmotic driver for the device.
Theeuwes U.S. Pat. No. 4,410,328 discloses an osmotically driven syringe/pump device. The osmotic driver in this device comprises a tablet of an osmotic solute, such as sodium chloride, coated with a semipermeable membrane having a fluid delivery orifice drilled therethrough. The influx of liquid into the osmotic engine, due to the homogeneous nature of the osmotic solute tablet, is constant and therefore the rate of delivery of solution from the osmotic engine into the driving compartment of the syringe is also constant. As a result, the syringe/pump device operates in a "steady state" or "tonic" mode which is characterized by a controlled although constant rate of drug delivery.
Pope et al U.S. Pat. No. 4,723,958 discloses an osmotically driven drug dispensing device. The delivery system provides an intermittent (i.e., on-off-on-off) drug delivery profile which is accomplished through the use of alternating layers of active drug and inert layers. In this device, similar to the device disclosed in U.S. Pat. No. 4,410,328, the influx of liquid into the osmotic driver, due to the homogeneous nature of the osmotic solute, is constant. Therefore, the rate at which the alternating layers are pushed out of the device is also constant. While this device provides some control over when the drug delivery pulses occur, there is no control over the rate at which the drug is delivered during the pulses.
Theeuwes U.S. Pat. No. 4,036,228 discloses an osmotic delivery device that uses a gas generating means, such as an effervescent couple, to deliver a drug which is insoluable in water at a controlled rate. The effervescent couple is osmotically active, causing water to premeate across the semipermeable outer wall. The water reacts with the effervescent couple to produce a gas which is pumped out of a delivery orifice. The pumped gas carries the insoluble drug to the desired environment of use.
While the above-described devices are useful for delivering many agents, and while they represent a valuable contribution to the delivery art, there has been a need in the art for a device which can deliver a beneficial agent to an environment of use at a continuous, controlled and variable rate of delivery.
Therefore, it is an object of the present invention to provide an osmotically driven syringe which can deliver a beneficial agent, such as a drug, to an environment of use at a controlled and non-constant delivery rate in order to optimize the treatment of a patient.